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Biomedical subjects

W Becker

Publications and source records attributed to W Becker.

At least 109 records · Page 6Linked to original sources
PubMed1999

Formation of bone around titanium implants placed into zero wall defects: pilot project using reinforced e-PTFE membrane and autogenous bone grafts.

BACKGROUND: Guided bone regeneration (GBR) frequently is used to augment implants with various types of bone defects. The defects often are grafted with different materials, yet there is insufficient evidence that these materials enhance bone-to-implant contacts. PURPOSE: The purpose of this pilot project was to test the principle of GBR to promote bone formation adjacent to commercially pure titanium implants placed within zero-wall defects. Histologic and histomorphometric measurements were used to evaluate new bone formation. MATERIALS AND METHODS: Under appropriate anesthesia, deep, wide defects were created within the mandibles of two large dogs. Buccolingual bone was removed to the depth of the defects leaving only the mesial and distal walls. Of the eight implants placed, three were augmented with titanium-reinforced expanded polytetrafluoroethylene (e-PTFE) barriers and autogenous bone chips. Three sites were augmented with barrier membranes only, and two sites were not augmented or grafted and served as controls. Seven months after surgery the dogs were sacrificed and block sections were taken for histologic evaluation. RESULTS: Histologic and histomorphometric measurements were used to evaluate new bone formation. Results from this evaluation revealed bone formation at the membrane-only sites and the membrane-plus-bone grafted sites. The bone grafts were completely incorporated by the newly formed marginal compact bone. For all treated sites, there was poor bone-to-implant contact. Histomorphometric measurements showed a trend toward greater bone formation at membrane-treated sites compared with control sites. However, autogenous bone grafting did not seem to affect the amount of newly regenerated bone. CONCLUSIONS: Within the limits of this pilot project, findings show trends toward bone healing, indicating constant and enhanced bone regeneration over the exposed implant. Bone contact to the implant surface generally was poor.

Animals↗
PubMed1999

Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism.

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.

Adipose Tissue↗
PubMed1999

Long-term evaluation of 282 implants in maxillary and mandibular molar positions: a prospective study.

BACKGROUND: Placement of implants into molar positions presents diagnostic, surgical and prosthetic challenges. There are few reported studies for implants placed into molar positions. The purpose of this prospective longitudinal study is to report long-term clinical outcomes for 282 implants placed into molar positions. METHODS: Two-hundred-twelve patients received 282 implants. Implant size, location, jaw shape, and bone quality were recorded for all implants placed into molar positions. Seventy implants were inserted in maxillae and 212 in mandibles. Marginal bone level changes in maxillae and mandibles were measured from non-standardized periapical radiographs taken at abutment connection and an average follow-up of 3.9 years. Mesial-distal implant measurements were made from the top of the implant cylinder to the first point of bone to implant contact. In mandibles, 39 implants were used for single molar replacements, 67 implants were placed into excellent bone quality (type I) and 113 were in good bone quality (type 11); 145 implants were placed into bone with moderate bone resorption (type B); 166 implants were placed in first molar positions and 46 in second molar sites. RESULTS: At 6 years the cumulative success rate (CSR) for mandibular implants is 91.5%, and the success rate from the 2 to 3 year follow-up is 100%. Of the 70 implants placed in maxillae, 16 replaced single molars. Thirty-two implants were placed in jaw shape B with type 2-bone quality. For maxillary implants, the 6-year CSR was 82.9% and the success rate remained steady at 100% after the 2 to 3 year follow-up. For maxillary implants, at abutment connection the average marginal bone level was 1.67 mm, while at follow-up it was 1.98 mm. These differences were statistically significant (P = 0.04), but are not considered to be clinically significant. For mandibular implants, at abutment connection the mean marginal bone level as measured from radiographs was 2.11 mm, and at follow-up was 2.02 mm. This slight gain in bone level was not statistically significant and is not considered to be clinically significant. CONCLUSIONS: Results of this prospective longitudinal study of implants placed into molar positions indicates favorable clinical outcomes. These CSR rates (91.5% mandibles, 82.9% maxillae) are less than what has been reported for implants placed into mandibular and maxillary anterior segments. Differences in outcomes between anterior and posterior locations may be related to bone quality and quantity.

Bone Density↗
PubMed1999

Quantification of intact quadriceps tendon, quadriceps tendon insertion, and suprapatellar fat pad: MR arthrography, anatomy, and cryosections in the sagittal plane.

OBJECTIVE: The purpose of this study was to quantify quadriceps tendon length, thickness, and insertion in relation to the suprapatellar fat pad. SUBJECTS AND METHODS: We used three methods to analyze the anatomy of intact quadriceps tendons and insertions into the patellar base: MR arthrography (53 knees with intact extensor mechanisms), gross anatomy (16 cadaveric knees), and cryosections (four cadaveric knees). With an electronic cursor, two observers independently quantified the extensor mechanism on midline sagittal T1-weighted spin-echo sequences acquired on a low-field-strength (0.23 T) scanner. RESULTS: On MR arthrograms, quadriceps tendon length, determined from the superior patellar pole to the most superior part of the suprapatellar recess, measured 49 +/- 7 mm in women and 50 +/- 9 mm in men. Thickness of quadriceps tendon at three sites (suprapatellar recess, center, and superior patellar pole) measured 7 +/- 1 mm in women and 8 +/- 1 mm in men. Thickness was significantly larger in men at all measurement locations. Quadriceps tendon insertion and the suprapatellar fat pad along the patellar base measured 16 +/- 2 and 6 +/- 2 mm, respectively, in women, and 18 +/- 3 and 7 +/- 2 mm, respectively, in men. CONCLUSION: On midline MR images, sagittal thickness of the quadriceps tendon and its insertion was significantly larger in men than in women. The prevalence of the suprapatellar fat pad was 100%.

Adipose Tissue↗
PubMed1999

Imaging osteomyelitis and the diabetic foot.

BACKGROUND: The clinical diagnosis of osteomyelitis and the diabetic foot is in most of the patients not possible without imaging the bone. The clinical problem is to diagnose infection as early, as reliable and as cheap as possible to prevent the possible longstanding and life-threatening complications. METHODS: For imaging a lot of different radiological and nuclear medicine methods are available. This article focuses on the possible results of conventional plain radiography and tomography, computed tomography and magnetic resonance imaging as radiological methods and on bone scan, autologous white blood cell scintigraphy with 111In-oxin or 99mTc-HMPAO, antigranulocyte antibodies, 99mTc-/111In-human immunoglobulin, 67Ga-citrate and 99mTc-nanocolloids. RESULTS: Different methods offer different answers. Radiological methods give detailed pathological answers, nuclear medicine methods answer questions of specificity such as leukocytic infiltration. CONCLUSIONS: If osteomyelitis is suspected, plain radiography should be the first, three phase bone scintigraphy the second and infection specific radiopharmaceuticals the third step of examination. Only in negative images with high clinical suspicion CT or MRI should be the final imaging procedure. In the diabetic foot imaging cascade should also start with plain radiography, followed by three phase bone scintigraphy or MRI. If clinically neuropathy is present specific nuclear medicine imaging should be performed.

Bone and Bones↗
PubMed1999

Correlation between radiation dose, synovial thickness, and efficacy of radiosynoviorthesis.

OBJECTIVE: To correlate the therapeutic efficacy of radiosynoviorthesis (RSO) to radiation doses achieved. METHODS: In 20 patients with known rheumatoid arthritis, radiosynoviorthesis was performed in 36 joints. Arthritis disease activity was assessed by "blood pool scintigraphy" (n = 29) score after injection of 370 MBq 99mTc-MDP, before and at 1, 2, and 5 months after the RSO in 12 patients. For semiquantitative measurements, a region-of-interest technique was applied. Synovial thickness and response to the RSO were evaluated by joint ultrasonography. Pain levels were evaluated semiquantitatively. Dosimetry (n = 20) was calculated using planar quantification according to the MIRD scheme. RESULTS: The mean radiation absorbed dose of 186Re-sulfate to the whole body was 5.3+/-2.7 cGy, liver 10.0+/-8.1 cGy, spleen 20.3+/-22.9 cGy, kidneys 9.4+/-11.4 cGy, and at the injected joints of the shoulder 120.5+/-32.2 Gy, hand 130.0+/-12.6 Gy, elbow 83.6+/-38.7 Gy, and talar/subtalar joint 84.1+/-30.7 Gy. In 7 cases, where mandatory immobilization of the joint was not possible, the dose to the lymph nodes (n = 25) was 25.9+/-53.8 Gy (maximum 189 Gy) and to single lymph nodes 14.6+/-11.2 Gy (maximum 63 Gy). The reduced doses to the synovia (at 40% leakage) were: 169Er-citrate 73.10+/-25.25 Gy; 90Y-citrate 59.25+/-46.45 Gy; 186Re-sulfate 65.40+/-32.55 Gy. In cases of complete immobilization, the dose to the lymph nodes was negligible: 169Er-citrate (n = 7), whole body dose 0.4 cGy, lymph nodes 2.3 Gy, finger joints 132.3+/-34.3 Gy; 90Y-citrate (n = 6), whole body dose 15.5 cGy, liver dose 26.5 cGy, splenic dose 11.9 cGy, kidney dose 67 cGy, joint knee joint dose 130.1 Gy. Regarding therapeutic effect, mean reduction of the 99mTc-MDP blood pool activity was 41% at first month, 48% at second month, 48% at the fifth month, 48% in larger joints, and 63% in finger joints. Three and 6 months after RSO, sonography showed a mean reduction in synovial swelling: in the knee joint 1.67 and 4.38 mm, respectively; in the larger joints (shoulder, elbow, hand, talar/subtalar) 0.88/1.93 mm; and in finger joints 0.53/1.76 mm. Clinically, best results were observed in the finger joints. CONCLUSION: 1. We observed a significantly higher radiation absorbed dose to the lymph nodes and lower dose to the synovia in the absence of joint immobilization. Immobilization of the joint is essential. 2. At 2 months after treatment, a significant reduction of blood pool activity and synovial swelling was observed, with further improvement in the following months, especially in the finger joints. 3. There is a strong correlation between the reduction of blood pool activity, synovial swelling, and improvement of pain.

Arthritis, Rheumatoid↗
PubMed1999

Periodontal regeneration: myth or reality?

One of the goals of periodontal therapy is regeneration. During the past 20 years, several materials and techniques have been developed and tested for enhancing periodontal regeneration. This paper evaluates flap debridement, allogenic and alloplastic grafting, and the use of nonresorbable and resorbable barrier membranes as regenerative techniques. One of the most predictable regenerative therapies is treatment of the three-walled intrabony defect. This defect can be repaired with 2 to 2.5 mm of bone fill and results in significant gains in clinical probing attachment and decreases in probing depths. There is a slightly greater improvement in periodontal measures with barrier membranes. Commercial preparations of allogenic bone and alloplastic fillers have a long, safe history of use and are primarily osteoconductive. They decrease probing depths and provide short-term gains in clinical attachment levels. Barrier membranes provide short-term evidence of improving Class II furcation invasions, however there is insufficient evidence that these improvements are sustained long-term. Class III furcations are not predictably treated by regenerative therapies. To date, there is an absence of clinical evidence that regenerative therapy increases the long-term life span of teeth.

Alveolar Bone Loss↗
PubMed1999

Radiolabeled peptides for targeting cholecystokinin-B/gastrin receptor-expressing tumors.

UNLABELLED: The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thyroid cancer (MTC) suggests widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies have demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs but also in a high percentage of small cell lung cancers, some ovarian cancers, astrocytomas and potentially a variety of adenocarcinomas. The aim of this study was to systematically screen and optimize, in a preclinical model and a pilot clinical study, suitable radioligands for targeting CCK-B receptors in vivo. METHODS: A variety of CCK/gastrin-related peptides, all bearing the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-PheNH2 or derivatives thereof, were studied. They were radioiodinated by the lodogen or Bolton-Hunter procedures. The peptides were members of the gastrin or CCK families, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in nude mice bearing subcutaneous human MTC xenografts. Diethylenetriamine pentaacetic acid (DTPA) derivatives of suitable peptides were synthesized successfully, and their preclinical and initial clinical evaluations were performed, labeled with 111In. RESULTS: All members of the CCK or gastrin families were stable in serum (with half-lives of several hours at 37 degrees C); nevertheless, the stability of those peptides bearing N-terminal pGlu residues or D-amino acids was significantly higher. In accordance with their comparably low affinity, nonsulfated members of the CCK family showed fairly low uptake in the tumor and other CCK-B receptor-expressing tissues. Sulfated CCK derivatives performed significantly better but also displayed a comparably high uptake in normal CCK-A receptor-expressing tissues. This effect was probably due to their similar affinity for both CCK-A and CCK-B receptors. Best tumor uptake and tumor-to-nontumor ratios were obtained with members of the gastrin family because of their selectivity and affinity for the CCK-B receptor subtype. Pilot therapy experiments in MTC-bearing animals showed significant antitumor efficacy compared with untreated controls. DTPA derivatives of minigastrin were successfully developed. In a pilot clinical study, radioiodinated and 111In-labeled derivatives showed excellent targeting of physiological CCK-B receptor-expressing organs, as well as all known tumor sites. CONCLUSION: CCK/gastrin analogs may be a useful new class of receptor-binding peptides for diagnosis and therapy of CCK-B receptor-expressing tumors, such as MTC or small cell lung cancer. Nonsulfated gastrin derivatives may be preferable because of their CCK-B receptor selectivity, hence lower accretion in normal CCK-A receptor-expressing organs.

Adult↗
PubMed1999

Substrate specificity of the ileal and the hepatic Na(+)/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters.

The substrate specificity of the ileal and the hepatic Na(+)/bile acid cotransporters was determined using brush border membrane vesicles and CHO cell lines permanently expressing the Na(+)/bile acid cotransporters from rabbit ileum or rabbit liver. The hepatic transporter showed a remarkably broad specificity for interaction with cholephilic compounds in contrast to the ileal system. The anion transport inhibitor diisothiocyanostilbene disulfonate (DIDS) is a strong inhibitor of the hepatic Na(+)/bile acid cotransporter, but does not show any affinity to its ileal counterpart. Inhibition studies and uptake measurements with about 40 different bile acid analogues differing in the number, position, and stereochemistry of the hydroxyl groups at the steroid nucleus resulted in clear structure;-activity relationships for the ileal and hepatic bile acid transporters. The affinity to the ileal and hepatic Na(+)/bile acid cotransport systems and the uptake rates by cell lines expressing those transporters as well as rabbit ileal brush border membrane vesicles is primarily determined by the substituents on the steroid nucleus. Two hydroxy groups at position 3, 7, or 12 are optimal whereas the presence of three hydroxy groups decreased affinity. Vicinal hydroxy groups at positions 6 and 7 or a shift of the 7-hydroxy group to the 6-position significantly decreased the affinity to the ileal transporter in contrast to the hepatic system. 6-Hydroxylated bile acid derivatives are preferred substrates of the hepatic Na(+)/bile acid cotransporter. Surprisingly, the 3alpha-hydroxy group being present in all natural bile acids is not essential for high affinity interaction with the ileal and the hepatic bile acid transporter. The 3alpha-hydroxy group seems to be necessary for optimal transport of a bile acid across the hepatocyte canalicular membrane. A modification of bile acids at the 3-position therefore conserves the bile acid character thus determining the 3-position of bile acids as the ideal position for drug targeting strategies using bile acid transport pathways.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Studies on the red marrow dosimetry in radioimmunotherapy: an experimental investigation of factors influencing the radiation-induced myelotoxicity in therapy with beta-, Auger/conversion electron-, or alpha-emitters.

Usually, the red marrow (RM) is the first dose-limiting organ in radioimmunotherapy. However, several studies have obtained only poor correlations between the marrow doses and the resulting toxicities. Furthermore, RM doses are mostly not determined directly but are derived from blood doses by assuming a ratio that is, over time for the respective conjugates, more or less constant between blood and marrow activities. The aim of this study was to determine, in a mouse model, this RM:blood activity ratio for various immunoconjugates, to investigate whether there may be differences between complete IgG and its fragments with various labels ((125/131)I versus (111)In, (88/90)Y, or 213Bi), and to analyze, in more detail, factors other than just total dose, such as dose rate or relative biological effectiveness factors, that may influence the resulting myelotoxicity. The maximum tolerated activities (MTAs) and doses (MTDs) of several murine, chimeric, and humanized immunoconjugates as complete IgG or fragments (F(ab)2 and Fab), labeled with beta(-)-emitters (such as 131I or 90Y), Auger electron-emitters (such as 125I or (111)In), or alpha-emitters (such as 213Bi) were determined in nude mice. Blood counts were monitored at weekly intervals; bone marrow transplantation was performed to support the assumption of the RM as dose-limiting. The radiation dosimetry was derived from biodistribution data of the various conjugates, accounting for cross-organ radiation; besides the major organs, the activities in the blood and bone marrow (and bone) were determined over time. Whereas no significant differences were found for the RM:blood ratios between various IgG subtypes, different radiolabels or various time points, differences were found between IgG and bi- or monovalent fragments: typically, the RM:blood ratios were approximately 0.4 for IgG, 0.8 for F(ab')2, and 1.0 for Fab'. Nevertheless, at the respective MTAs, the RM doses differed significantly between the three conjugates: e.g., with 131I-labeled conjugates, the maximum tolerated activities were 260 microCi for IgG, 1200 microCi for F(ab)2, and 3 mCi for Fab, corresponding to blood doses of 17, 9, and 4 Gy, respectively. However, initial dose rates were 10 times higher with Fab as compared to IgG, and still 3 times higher as compared to F(ab)2; interestingly, all three deliver approximately 4 Gy within the first 24 h. The MTDs of all three conjugates were increased by BMT by approximately 30%. Similar observations were made for 90Y-conjugates. Higher RM doses were tolerated with Auger-emitters than with conventional beta(-)-emitters, whereas the MTDs were similar between alpha- and beta(-)-emitters. In accordance to dose rates never exceeding those occurring at the single injection MTA, two subsequent injections of two doses of 80% of the single shot MTA of 131I- or 90Y-labeled Fab' and two doses of 100% of the single shot MTA of 213Bi-labeled Fab' were tolerated without increased lethality, if administered 24-48 h apart. In contrast, reinjection of bivalent conjugates was not possible within 6 weeks. These data suggest that the RM:blood activity ratios differ between IgG and fragments, although there is no anatomical or physiological explanation for this phenomenon at this point. In contrast to the current opinion, indication for a strong influence of the dose rate (or dose per unit time), not only total dose, on the resulting toxicity is provided, whereas the influence of high-linear energy transfer (alpha and Auger/conversion electrons) versus low-linear energy transfer (beta and gamma) type radiation seems to be much lower than expected from previous in vitro data. The lower myelotoxicity of Auger-emitters is probably due to the short path length of their low-energy electrons, which cannot reach the nuclear DNA if the antibody is not internalized into the stem cells of the RM.

Alpha Particles↗